Mass spectroscopy is an analytical technique used to identify the mass-to-charge (m/Z) ratio of ions and ion fragments produced when a sample is ionized and parent ions are sufficiently energized to fragment. Identifying the mass-to-charge ratio of the ion fragments provides information about the parent ion. Mass spectroscopy systems use electric and/or magnetic fields to guide the ions fragments along trajectories that depend on their mass-to-charge ratios. Many systems include “ion guides” and “ion traps,” in which the ion trajectories are stable along some or all coordinate directions only for a selected range of mass-to-charge ratios.
Many ion traps, such as quadrupole ion traps, apply a combination of radio-frequency (RF) and direct-current (DC) voltages to electrodes to form the trapping fields. The relative magnitude of the RF and DC voltages determine the range of mass-to-charge ratios that correspond to stable trajectories. Those ions that are stable undergo oscillations within the trap at frequencies that depend on their mass-to-charge ratio. In some cases, the ion trap may further apply an alternating-current (AC) voltage to the electrodes to induce resonant excitation of a selected subset of the trapped ions, for the purpose of either inducing collisions that dissociate those ions or ejecting them from the trap.
One common ion trap configuration is a three-dimensional quadrupole trap (3D-IT), which involves a ring electrode and two end cap electrodes. Most commonly, an RF potential is applied to the ring electrode with the end cap electrodes held at ground to generate the trapping fields. Another configuration is a linear ion trap (LIT), which involves an extended set of electrodes to transversely confine ions and electrostatic “plugs” at opposite ends of the trap to axially confine the ions. RF potentials are applied to the extended set of electrodes to generate quadrupole-type trapping fields along the transverse coordinates and DC potentials at the ends to prevent ions from diffusing out either end of the trap. The volume in which the ions are significantly influenced by the DC end potentials is generally a small fraction of the volume ions occupy in the LIT so that the ion's trapping motion is described by the transverse coordinates alone and the LIT is therefore also denoted a two-dimensional ion trap. Combining the transverse RF quadrupolar potential with an additional DC potential that is applied between electrodes in different axial regions to produce a static harmonic trapping potential along the axial coordinate generates another three-dimensional trap, referred to as a harmonic linear trap (HLT). Examples of prior art for the HLT are Prestage et al., J. Applied Phys. 66, 1013 (1989) and Raizen et al., Phys. Rev. A 45, 6493 (1992). As a technical aside, almost all physical LITs are in fact HLTs with very weak quadratic potentials. Details of such radio-frequency ion traps are well known in the art. See, for example, U.S. Pat. No. 4,540,884 to Stafford et al., U.S. Pat. No. 5,420,425 to Bier et al., and U.S. Pat. No. 5,179,278 to Douglas.
Furthermore, many mass spectroscopy systems are hybrids in which ion guides and ion traps are arranged to transfer ions between themselves and to other mass analysis devices such as time-of-flight (TOF), Fourier transform ion cyclotron resonance (FT-ICR) or electrostatic (e.g., “Orbitrap”) mass spectrometers. Components of hybrid systems may offer different functionality in the overall molecular analysis, for example, an ion guide may accumulate ions, and an ion trap may isolate and fragment ions, while a TOF or other mass analysis device may provide high resolution m/Z measurements.
To provide additional information about a parent ion, it may be preferable to perform multiple stages of isolating ions having a selected mass-to-charge ratio and fragmenting those ions. For example, a first stage of mass spectrometry may be used to select a primary ion of interest, for example, a molecular ion of a particular biomolecular compound such as a peptide, and that ion is caused to fragment by increasing its internal energy, for example, by colliding the ion with a neutral molecule. A second stage of mass spectrometry may then be used to analyze the mass-to-charge ratios of the fragment ions. Often the structure of the primary ion can be determined by interpreting the fragmentation pattern. This process is typically referred to as an MS/MS or MS(2) analysis. The MS/MS analysis improves the recognition of a compound with a known pattern of fragmentation and also improves specificity of detection in complex mixtures, where different components give overlapping peaks in a single stage of MS. Further information about the parent ion may be determined by implementing additional stages of mass-to-charge isolation and fragmentation, something that is typically referred to as MS(N) analysis.
In most MS(N>1) systems, a specific ion fragment is first isolated by ejecting all other ion fragment m/Z values and the isolated ion is then induced to fragment. The ejection of ions or ion fragments that are not being selected at a particular stage of the MS(N) analysis results in a loss of sensitivity or a loss of information which may otherwise be derived from the ejected ion fragments. To retain ion fragments not selected at a particular stage of the MS(N) analysis for use at other stages of the MS(N) analysis, a multiple stage mass spectrometer may be used. Such a spectrometer is described in PCT Publication WO 01/15201 A2 and U.S. Pat. No. 6,483,109 by Reinhold and Verentchikov, and U.S. Pat. No. 7,071,464 by Reinhold, the contents of which are incorporated herein by reference. These documents disclose different dynamical methods for selecting an ion for fragmentation by m/Z-selective transfer from a population of trapped ions such that both the ions transferred and the ions not transferred remain available for fragmentation analyses.
U.S. Pat. No. 7,071,464 teaches that one class of methods for selective transfer involves generating spatially localized modifications in an axially extended trapping field. These field modifications generate axial forces on the ion which increase with the amplitude of the ion's transverse oscillation and vanish for ions with no transverse amplitude. Combining the field modifications with a static DC potential to block unexcited ions creates a region of the axially extended RF trapping field which selectively transmits ions with transverse oscillation amplitude. This region was denoted an excitation gate. U.S. Pat. No. 7,071,464 discloses a method of m/Z-selection in which resonance excitation at specific frequencies selectively increases the transverse oscillation amplitude of a subset of the confined ions in a linear ion trap region displaced from the excitation gate. The entire ion population is then directed into the excitation gate and the subset of ions that were transversely excited pass through the gate while unexcited ions are blocked. The combination of a linear ion trap (LIT) region and localized field modification or excitation gate will herein be referenced as an excitation gate trap (EGT).
The EGT described could be a component of many hybrid MS systems. For example, in a quadrupole-TOF system (an MS/MS system consisting of an ion source, a quadrupole mass filter, a collision cell and a TOF mass analyzer) an EGT could replace the mass filter. Selected ions from an ion ensemble accumulated in the LIT would be resonance excited and then directed to transfer through the excitation gate and accelerated into the collision cell. These ions would fragment and the fragments would be mass-analyzed by the TOF (in the same manner as with current quadrupole-TOF instruments). Ions not resonance excited remain trapped for subsequent excitation and transfer. The advantage of using the excitation gate as opposed to a mass filter for m/Z selection is sensitivity. The transfer of ions in a limited m/Z range leaves the rest of the trapped ions in the LIT available for subsequent transfer and MS(2) analysis. In contrast, when the mass filter transmits a limited m/Z range from an ion beam to the collision cell the ions not transmitted are lost to unstable trajectories. If ions in the incident flux can be accumulated in the EGT and multiple components selectively MS(2) analyzed, one would be able to MS(2) analyze ions with the EGT that are currently ejected with the mass filter. In this application a technical challenge is to make the EGT operate with the highest possible incident flux of ions from the ion source.